Enhancement of Neonatal Rat Ductal Responsiveness to Prostaglandin E2 after Maternal Treatment with Enalapril or Captopril.

Abstract

ABSTRACT. This work was conducted to determine whether the angiotensin-converting enzyme inhibitors (ACEIs) (enalapril and captopril) administered to mother rats prenatally can potentiate a re-opening of the neonatal ductus arteriosus (DA) induced by prostaglandin E 2 (PGE 2 ) after postnatal closure. A subcutaneous injection of PGE 2 (4 µg) was administered to newborn rats 3 hr after a Cesarean delivery from females which had been orally given 0.1, 1 or 10 mg/kg/day of enalapril or 15 or 150 mg/kg/day of captopril from day 14 to day 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in the newborn rats of mothers who were transplacentally administered these agents compared to the controls, except at the low dose (0.1 mg/kg) group of enalapril. We found that the level in the neonatal lungs of 15-hydroxy prostaglandin dehydrogenase, a key enzyme that catalyzes PGE 2 to convert it to its inactive metabolite 15-keto-PGE 2 , was not affected after maternal treatment with enalapril or captopril. These results indicate that the increased ductal responsiveness to PGE 2 in newborn rats was a common response after maternal ACEI treatment, but the catabolism of PGE 2 in the lungs did not contribute to this response. -KEY WORDS: ductus arteriosus, PGE 2 catabolism, re-opening.J. Vet. Med. Sci. 60(8): 989-991, 1998 that the maternal administration of ACEIs such as enalapril and captopril can potentiate the neonatal ductal responsiveness to PGE 2 after the postnatal closure of the DA and can inhibit the catabolism of PGE 2 in the lungs. We investigated the effects of enalapril and captopril on the re-opening of the DA as well as the effect of these agents on the activity in the lungs of 15-hydroxy prostaglandin dehydrogenase (15-PGDH), a key enzyme which catalyzes the initial reactions converting the biologically active PGE 2 to its inactive metabolite, 15-keto-PGE 2 .Female Crj: Wistar rats, 10-12 weeks old at the time of mating, were used. They were maintained on a commercial diet (CE-2, Clea Japan, Tokyo) and tap water ad libitum, and kept in a room at a temperature of 22 ± 3°C with a relative humidity of 55 ± 10%. Three females were placed with a male overnight and examined the next morning for the presence of sperm in the vaginal smear. The day on which sperm was found was designated as day 0 of gestation, and the females were caged individually thereafter.In the first experiment, the effects of prenatal enalapril and captopril treatments on the re-opening of the DA induced by PGE 2 was examined. Enalapril (0.1, 1, 10 mg/ kg/day) or captopril (15, 150 mg/kg/day) administration was carried out from day 14 to day 20 of gestation. Pregnant females given only saline served as the controls. The rats were killed by decapitation at 1 p.m. on day 21 of gestation at least 24 hr after the last drug administration, and the newborn pups were immediately obtained by Cesarean delivery. Only male pups were used in this study. Th...

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

“…However, prenatal exposure to ACEIs might inhibit ductal closure via the effects of ACEIs on the fetal bradykinin-prostaglandin system [10]. The present study also supports the view that ACEIs such as enalapril inhibit the maturation of the DA, and that the DA responsiveness to PGE2 thereby increased [30], and this mechanism may be partly responsible for the development of PDA, because PDA often occurs in immature infants [8].…”

“…The use of ACEIs during the second and third trimesters of pregnancy has been associated with fetal and neonatal morbidity, including intrauterine growth retardation, oligohydramnios, reversible and irreversible renal failure and patent ductus arteriosus (PDA) [2,23]. In a previous study, we suggested that the use of ACEIs may cause PDA based on the observations that re-opening activity of the DA increased significantly after maternal treatment with enalapril or captopril [30] and spontaneous closure of the DA was partly inhibited after treatment with enalapril [28,29]. However, prenatal exposure to ACEIs might inhibit ductal closure via the effects of ACEIs on the fetal bradykinin-prostaglandin system [10].…”